Abnormal Serum Biochemical Results and Mitochondrial Damage of Lymphocytes in Patients with Schizophrenia and SARS-CoV-2 Infection: A Retrospective Study.

Purpose: In this study, we investigated the differences in clinical biochemical values and mitochondrial mass between schizophrenia patients with and without COVID-19, so as to provide assistance to the treatment and management of COVID-19 positive patients with schizophrenia. Patients and methods: We undertook an exploratory, retrospective review of patient data from Dec. 6, 2022, to Jan. 31, 2023. A total of 1696 inpatients with psychosis (921 schizophrenia patients and 775 diagnosed with other mental diseases) during this period were identified. Finally, 60 schizophrenia patients were enrolled in our study, and 20 of them were infected with syndrome coronavirus 2 (SARS-CoV-2). The serum biochemical levels and single-cell mitochondrial mass (SCMM) of the T lymphocytes of all schizophrenia patients were analyzed. Results: The serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine (Cr) and lactate dehydrogenase (LDH) were significantly higher in schizophrenia patients with COVID-19 (SCZ-C) group. In addition, the SCZ-C group showed lower CD3+, CD3+CD4+ and CD3+CD8+ cell counts and higher SCMM of T lymphocytes compared to SCZ group. Furthermore, positive correlations were found between the T-cell subpopulation counts and positive symptom scores on the Positive and Negative Syndrome Scale (PANSS). Conclusion: Our study findings showed that schizophrenia patients with COVID-19 have a phenotype of mitochondrial damage in T lymphocytes and higher serum levels of AST, ALP, Cr and LDH, which might provide evidence for treating individuals with schizophrenia during subsequent spread of infectious disease.

GDI2 deletion alleviates neurodegeneration and memory loss in the 5xFAD mice model of Alzheimer's disease.

Accumulation of insoluble deposits of amyloid ß-peptide (Aß), derived from amyloid precursor protein (APP) processing, represents one of the major pathological hallmarks of Alzheimer's disease (AD). Perturbations in APP transport and hydrolysis could lead to increased Aß production. However, the precise mechanisms underlying APP transport remain elusive. The GDP dissociation inhibitor2 (GDI2), a crucial regulator of Rab GTPase activity and intracellular vesicle and membrane trafficking, was investigated for its impact on AD pathogenesis through neuron-specific knockout of GDI2 in 5xFAD mice. Notably, deficiency of GDI2 significantly ameliorated cognitive impairment, prevented neuronal loss in the subiculum and cortical layer V, reduced senile plaques as well as astrocyte activation in 5xFAD mice. Conversely, increased activated microglia and phagocytosis were observed in GDI2 ko mice. Further investigation revealed that GDI2 knockout led to more APP co-localized with the ER rather than the Golgi apparatus and endosomes in SH-SY5Y cells, resulting in decreased Aß production. Collectively, these findings suggest that GDI2 may regulate Aß production by modulating APP intracellular transport and localization dynamics. In summary, our study identifies GDI2 as a pivotal regulator governing APP transport and process implicated in AD pathology; thus highlighting its potential as an attractive pharmacological target for future drug development against AD.

Postoperative plasma presepsin as a biomarker of postoperative infectious complications in different surgical departments: A meta-analysis and systematic review.

BACKGROUND: High rates of postoperative infection persist after different surgical procedures, encompassing surgical site infections (SSIs), remote infections, sepsis, and septic shock. Our aim was to assess presepsin's diagnostic accuracy for postoperative infections in patients across surgical procedures. METHOD: We conducted a comprehensive search in seven databases, extracting data independently. Using STATA 14.0, we calculated pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and Under the receiver operator curve and 95 â€‹% confidence interval (AUC, 95 â€‹% CI) as primary outcomes, with secondary outcomes involving sensitivity and specificity in subgroup analyses. RESULTS: This meta-analysis of 14 studies (1891 cases) evaluated presepsin's diagnostic value for postoperative infectious complications. Results include sensitivity of 77 â€‹% (70-83), specificity of 81 â€‹% (71-88), DOR of 14 (8-26), AUC of 84 (80-87), PLR of 4 (3-6), and NLR of 0.28 (0.21-0.38). Presepsin exhibits promise as a diagnostic tool for postoperative infections. CONCLUSION: In summary, compared to conventional markers like C-reactive protein (CRP) and procalcitonin (PCT), presepsin demonstrated superior sensitivity and specificity for detecting postoperative infectious complications across various surgical procedures.

Application of combined preoperative indocyanine green lymphography and ultrasonography for low-pressure vein localization in secondary lymphedema surgery for breast cancer.

BACKGROUND: This study aimed to investigate the value of preoperative indocyanine green (ICG) lymphography combined with ultrasonography for low-pressure vein localization in secondary lymphedema surgery for breast cancer. METHODS: A total of 29 patients who were admitted to the breast surgery department of our hospital from July 2019 to May 2021 were included in this study. All patients received preoperative reverse lymphography and ultrasonography for low-pressure vein in lymphedema surgery. Three arm circumferences were measured before surgery, 6 months after surgery, and 12 months after surgery for comparison with the healthy limb at the same time. RESULTS: Arm circumference at 12 months after surgery was significantly different from those at the preoperative period and 6 months after surgery (P < 0.05). However, this parameter after surgery was still significantly higher than that of the healthy limb (P < 0.05). CONCLUSIONS: The application of preoperative ICG lymphography combined with ultrasonography for low-pressure vein localization before surgery can greatly shorten operation duration by reducing the number of ineffective incisions and improving the probability of vein-lymphatic vessel matching, while ensuring the postoperative efficacy for patients.

Diagnostic Accuracy of Procalcitonin for Infection After Adult Liver Transplantation: A Meta-Analysis and Systematic Review.

Background: Post-operative infection remains a major cause of morbidity and mortality in adults early after liver transplantation (LT). Procalcitonin (PCT) may be a good test method for early diagnosis of post-operative infection and determining its severity. This study was performed to assess the diagnostic accuracy of PCT as a biomarker for infection after LT. Patients and Methods: A meta-analysis and systematic review was conducted for studies reporting diagnostic performance of PCT for infection in adults after LT. Observational studies were evaluated for their reporting of diagnostic accuracy, relevance, and quality. Results: Ten eligible studies assessing 730 patients were included in this meta-analysis and systematic review summarizing the diagnostic value of PCT for post-operative infection in adult liver transplantation. Pooled sensitivity and specificity with corresponding 95% confidence interval were 69% (95% confidence interval [CI], 54-81; heterogeneity I2 = 82.4%) and 88% (95% CI, 82-92; I2 = 52.7%), respectively. The diagnostic odd ratio (DOR) was 16 (95% CI, 10-25; I2 = 76.4%). The summary receiver operator characteristic (SROC) of PCT for post-operative infection was 0.88. There was a wide range of variability in the cutoff values, ranging from 0.22 to 42.80 ng/mL. Heterogeneity was reduced by excluding studies that focused on pediatric LT recipients. Conclusions: Procalcitonin is a moderately accurate diagnostic marker for post-operative infection in adult LT. Additionally, the diagnostic performance can be improved by combining it with other inflammatory biomarkers. This article provides the research direction for post-operative infection control.

Mice with the Rab10 T73V mutation exhibit anxiety-like behavior and alteration of neuronal functions in the striatum.

Hyperphosphorylated Rab10 has been implicated in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. However, the neurophysiological function of the evolutionarily conserved Thr73 phosphorylation of Rab10 remains poorly understood. Here, we generated a novel mouse model expressing the non-phosphorylatable T73V mutation of Rab10 and performed a comprehensive series of neurological analyses, including behavioral tests, synaptic evaluations, neuronal and glial staining, assessments of neurite arborization and spine morphogenesis. The Rab10 T73V mutantmice exhibited a characteristic anxiety-like phenotype with other behavioral modules relatively unaffected. Moreover, Rab10 T73V mutant mice displayed striatum-specific synaptic dysfunction, as indicated by aberrantly increased expression levels of synaptic proteins and impaired frequencies of miniature inhibitory postsynaptic currents. The genetic deletion of Rab10 phosphorylation enhanced neurite arborization and accelerated spine maturation in striatal medium spiny neurons. Our findings emphasize the specific role of intrinsic phospho-Rab10 in the regulation of the striatal circuitry and its related behaviors.

REEP1 Preserves Motor Function in SOD1G93A Mice by Improving Mitochondrial Function via Interaction with NDUFA4.

A decline in the activities of oxidative phosphorylation (OXPHOS) complexes has been consistently reported in amyotrophic lateral sclerosis (ALS) patients and animal models of ALS, although the underlying molecular mechanisms are still elusive. Here, we report that receptor expression enhancing protein 1 (REEP1) acts as an important regulator of complex IV assembly, which is pivotal to preserving motor neurons in SOD1G93A mice. We found the expression of REEP1 was greatly reduced in transgenic SOD1G93A mice with ALS. Moreover, forced expression of REEP1 in the spinal cord extended the lifespan, decelerated symptom progression, and improved the motor performance of SOD1G93A mice. The neuromuscular synaptic loss, gliosis, and even motor neuron loss in SOD1G93A mice were alleviated by increased REEP1 through augmentation of mitochondrial function. Mechanistically, REEP1 associates with NDUFA4, and plays an important role in preserving the integrity of mitochondrial complex IV. Our findings offer insights into the pathogenic mechanism of REEP1 deficiency in neurodegenerative diseases and suggest a new therapeutic target for ALS.

Calprotectin as a diagnostic marker for sepsis: A meta-analysis.

Introduction: Sepsis is a life-threatening condition, and biomarkers are needed to diagnose sepsis fast and accurately. We aimed to perform this meta-analysis to investigate the diagnostic value of calprotectin on sepsis in critically ill patients. Methods: The investigators searched MEDLINE, Embase, Web of Science and Cochrane Library. Studies were included if they assessed the diagnostic accuracy of serum calprotectin for sepsis in intensive care unit (ICU). We estimated its diagnostic value and explored the source of heterogeneity. The bivariate model and the hierarchical summary receiver operating characteristic (HSROC) curve were used in the meta-analysis. Results: Six records assessing 821 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were separately as 0.77, 0.85, 5.20, 0.27, respectively. The Fagan's nomogram showed post-test probabilities of 91% and 35% for positive and negative outcomes, respectively. Subgroup analysis indicated that sepsis definition could be a possible source of heterogeneity, but there's no sufficient data to investigate sepsis-3 definition. Sensitivity analysis suggested that two studies could affect the stability of pooled results. Conclusion: On the basis of our meta-analysis, calprotectin is a helpful marker for early diagnosis of sepsis on ICU admission.

Postoperative serum myoglobin as a predictor of early allograft dysfunction after liver transplantation.

Background: Early allograft dysfunction (EAD) is a common postliver transplant complication that has been associated with graft failure and risk for poor prognosis. There are many risk factors for the incidence of EAD after liver transplantation (LT). This study investigated whether elevated postoperative myoglobin (Mb) increases the incidence of EAD in liver transplanted recipients. Methods: A total of 150 adult recipients who measured Mb within 3 days after liver transplantation between June 2019 and June 2021 were evaluated. Then, all patients were divided into two groups: the EAD group and the non-EAD group. Univariate and multivariate logistic regression analyses were performed, and receiver operating characteristic curves (ROCs) were constructed. Results: The incidence of EAD was 53 out of 150 patients (35.3%) in our study. Based on the multivariate logistic analysis, the risk of EAD increased with elevated postoperative Mb (OR = 1.001, 95% CI 1.000-1.001, P = 0.002). The Mb AUC was 0.657, and it was 0.695 when combined with PCT. When the subgroup analysis was conducted, the AUC of serum Mb prediction was better in patients whose preoperative model for end-stage liver disease score ≤ 15 or operative time ≥ 10 h (AUC = 0.751, 0.758, respectively, or 0.760, 0.800 when combined with PCT). Conclusion: Elevated Mb significantly increased the risk of postoperative EAD, suggesting that postoperative Mb may be a novel predictor of EAD after liver transplantation.The study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100044257, URL: http://www.chictr.org.cn).

Highly tumoricidal efficiency of non-oxidized MXene-Ti3C2Tx quantum dots on human uveal melanoma.

Uveal melanoma (UM) is a highly malignant intraocular tumor with poor prognosis. Current topical ophthalmic therapies purpose to conserve the eye and useful vision. Due to the risks and limited clinical benefits, the topical treatments of UM remain challenging and complex. In this study, newly developed non-oxidized MXene-Ti3C2Tx quantum dots (NMQDs-Ti3C2Tx) are proposed for UM treatment. Surprisingly, NMQDs-Ti3C2Tx shows significant tumor-killing effects on UM cells in a dose-dependent manner and causes severe necrosis near the injection site on the xenograft UM tumor model. Moreover, NMQDs-Ti3C2Tx exhibits excellent biocompatibility with normal retina pigment epithelium (RPE) cells and does not cause any damage in C57BL/6 mice eyes. Mechanistically, NMQDs-Ti3C2Tx inhibits the proliferation, invasion, and migration of UM cells via its desirable reactive oxygen species (ROS) generation ability, which causes lipid peroxidation and mitophagy, triggering cell ferroptosis. Furthermore, NMQDs-Ti3C2Tx is detected accumulating in autolysosomes which exacerbates cell death. This work provides new light on the topical treatment of UM.

Discovering Innate Driver Variants for Risk Assessment of Early Colorectal Cancer Metastasis.

Metastasis is the main fatal cause of colorectal cancer (CRC). Although enormous efforts have been made to date to identify biomarkers associated with metastasis, there is still a huge gap to translate these efforts into effective clinical applications due to the poor consistency of biomarkers in dealing with the genetic heterogeneity of CRCs. In this study, a small cohort of eight CRC patients was recruited, from whom we collected cancer, paracancer, and normal tissues simultaneously and performed whole-exome sequencing. Given the exomes, a novel statistical parameter LIP was introduced to quantitatively measure the local invasion power for every somatic and germline mutation, whereby we affirmed that the innate germline mutations instead of somatic mutations might serve as the major driving force in promoting local invasion. Furthermore, via bioinformatic analyses of big data derived from the public zone, we identified ten potential driver variants that likely urged the local invasion of tumor cells into nearby tissue. Of them, six corresponding genes were new to CRC metastasis. In addition, a metastasis resister variant was also identified. Based on these eleven variants, we constructed a logistic regression model for rapid risk assessment of early metastasis, which was also deployed as an online server, AmetaRisk (http://www.bio-add.org/AmetaRisk). In summary, we made a valuable attempt in this study to exome-wide explore the genetic driving force to local invasion, which provides new insights into the mechanistic understanding of metastasis. Furthermore, the risk assessment model can assist in prioritizing therapeutic regimens in clinics and discovering new drug targets, and thus substantially increase the survival rate of CRC patients.

A nomogram prediction model for sternal incision problems.

Presently, the incidence and mortality rates of sternal incision problems (SIPs) after thoracotomy remain high, and no effective preventive measures are available. The data on 23 182 patients at Xinqiao Hospital, Army Medical University treated with median sternotomy from 1 August 2009 to 31 July 2019 were retrospectively reviewed. A prediction model of SIPs after median thoracotomy was established using R software and then validated using the bootstrap method. Next, the validity and accuracy of the model were tested and evaluated. In total, 15 426 cases met the requirements of the present study, among which 309 cases were diagnosed with SIPs, with an incidence rate of 2%. The body mass index (BMI), intensive care unit (ICU) time, diabetes mellitus, and revision for bleeding were identified as independent risk factors for postoperative SIPs. The nomogram model achieved good discrimination (73.9%) and accuracy (70.2%) in predicting the risk of SIPs after median thoracotomy. Receiver operating characteristic curve analysis showed that the area under curve of the model was 0.705 (95% confidence interval [CI]: 0.746-0.803); the Hosmer-Lemeshow test showed that χ2  = 6.987 and P = 0.538, and the fitting degree of the calibration curve was good. Additionally, the clinical decision curve showed that the net benefit of the model was greater than 0, and the clinical application value was high. The nomogram based on BMI, ICU time, diabetes mellitus, and revision for bleeding can predict the individualised risk of SIPs after median sternotomy, showing good discrimination and accuracy, and has high clinical application value. It also provides significant guidance for screening high-risk populations and developing intervention strategies.

Long non-coding RNA NORAD promotes the prostate cancer cell extracellular vesicle release via microRNA-541-3p-regulated PKM2 to induce bone metastasis of prostate cancer.

BACKGROUND: Bone metastasis is the leading cause of mortality and reduced quality of life in patients with metastatic prostate cancer (PCa). Long non-coding RNA activated by DNA damage (NORAD) has been observed to have an abnormal expression in various cancers. This article aimed to explore the molecular mechanism underlying the regulatory role of NORAD in bone metastasis of PCa. METHODS: NORAD expression in clinical PCa tissues and cell lines was detected with the application of qRT-PCR. Cancer cells were then transfected with plasmids expressing NORAD, after which Transwell assay and CCK-8 assay were carried out to detect proliferation, migration, and bone metastasis of PCa. NORAD downstream target molecules were screened through bioinformatics analysis, followed by further verification using dual luciferase assay. Extracellular vesicles (EVs) were labeled with PKH67 and interacted with bone marrow stromal cells. The gain- and loss-function method was applied to determine the internalization and secretion of PCa cells-derived EVs under the intervention of downstream target molecules or NORAD. RESULTS: PCa tissues and cell lines were observed to have a high expression of NORAD, particularly in tissues with bone metastasis. NORAD knockdown resulted in reduced secretion and internalization of EVs, and suppressed proliferation, migration, and bone metastasis of PCa cells. It was indicated that NORAD interacted with miR-541-3p, leading to the upregulation of PKM2. Forced expression of PKM2 promoted the transfer of PKH67-labeled EVs to bone marrow stromal cells. CONCLUSIONS: NORAD might serve as a ceRNA of miR-541-3p to promote PKM2 expression, thereby enhancing the development of bone metastasis in PCa by promoting internalization and transfer of EVs of cancer cells, providing an insight into a novel treatment for the disorder.

Meta-omics characteristics of intestinal microbiota associated to HBeAg seroconversion induced by oral antiviral therapy.

Tenofovir and entecavir are currently designated as the preferred oral antiviral drugs for chronic hepatitis B. However, only less than 40% of patients can achieve HBeAg seroconversion. We aim at investigating the role of intestinal microbiome in HBeAg seroconversion induced by oral antiviral therapy and describe multi-omics characteristics of HBeAg seroconversion associated intestinal flora. In this study, we prospectively collected fecal samples at baseline from the patients with HBeAg positive chronic hepatitis B who would have oral antiviral therapy. 16S rDNA sequencing and metabolomics were performed. We identified HBeAg seroconversion-related microbial signature and constructed prediction model for HBeAg seroconversion. Thirty-seven of these subjects achieved HBeAg seroconversion within 156 weeks after the initiation of oral antiviral therapy, while 41 subjects remained HBeAg positive even after over 156 weeks of therapy. A computational statistical and machine learning approach allowed us to identify a microbial signature for HBeAg seroconversion. Using random forest method, we further constructed a classifier based on the microbial signature, with area under curve being 0.749 for the test set. Patients who achieved HBeAg seroconversion tended to have lower abundance of certain fecal metabolites such as essential amino acids, and several dipeptides. By analyzing the fecal microbiota from the patients with and without HBeAg seroconversion, we showed intestinal microbiome play a critical role in HBeAg seroconversion induced by oral antiviral therapy. We also identified intestinal microbial signature that is associated with HBeAg seroconversion after oral antiviral therapy.

Resection and reconstruction of a giant primitive neuroectodermal tumour of the abdominal wall with an ultra-long lateral circumflex femoral artery musculocutaneous flap: a case report.

BACKGROUND: Primitive neuroectodermal tumours are clinically rare. Here, we report a case of a large peripheral primitive neuroectodermal tumour of the abdominal wall. The defect was reconstructed with the longest lateral circumflex femoral artery musculocutaneous flap reported to date. CASE PRESENTATION: A 15-year-old male suffered rupture and bleeding of an abdominal wall mass with a volume of approximately 23*18*10 cm3, involving the whole layer of the abdominal wall. Pathological examination revealed a peripheral primitive neuroectodermal tumour. The tumour was removed via oncologic resection, and the abdominal wall was reconstructed with a bilateral 44*8 cm2 lateral circumflex femoral artery musculocutaneous flap combined with a titanium polypropylene patch. The patient had smooth recovery postoperative, and the functions of the donor and recipient areas of the flap were not significantly affected. CONCLUSION: In this case report, we describe a rare primitive neuroectodermal tumour of the abdominal wall, which invaded almost the entire abdominal wall due to delay of treatment. After thoroughly removing the tumour, we immediately reconstructed the abdominal wall with an ultra-long lateral circumflex femoral artery musculocutaneous flap and achieved better appearance and function after the operation. This case suggests that we should adopt an integrated scheme of surgery combined with radiotherapy and chemotherapy in the treatment of peripheral primitive neuroectodermal tumours. Under the premise of determining the blood supply, the lateral circumflex femoral artery musculocutaneous flap can be cut to a sufficient length.

Role of endogenous ouabain in the etiology of bipolar disorder.

BACKGROUND: Bipolar disorder is a severe psychiatric illness with poor prognosis and problematic and suboptimal treatments. Understanding the pathoetiologic mechanisms may improve treatment and outcomes. DISCUSSION: Dysregulation of cationic homeostasis is the most reproducible aspect of bipolar pathophysiology. Correction of ionic balance is the universal mechanism of action of all mood stabilizing medications. Recent discoveries of the role of endogenous sodium pump modulators (which include 'endogenous ouabain') in regulation of sodium and potassium distribution, inflammation, and activation of key cellular second messenger systems that are important in cell survival, and the demonstration that these stress-responsive chemicals may be dysregulated in bipolar patients, suggest that these compounds may be candidates for the coupling of environmental stressors and illness onset. Specifically, individuals with bipolar disorder appear to be unable to upregulate endogenous ouabain under conditions that require it, and therefore may experience a relative deficiency of this important regulatory hormone. In the absence of elevated endogenous ouabain, neurons are unable to maintain their normal resting potential, become relatively depolarized, and are then susceptible to inappropriate activation. Furthermore, sodium pump activity appears to be necessary to prevent inflammatory signals within the central nervous system. Nearly all available data currently support this model, but additional studies are required to solidify the role of this system. CONCLUSION: Endogenous ouabain dysregulation appears to be a reasonable candidate for understanding the pathophysiology of bipolar disorder.

Quetiapine Attenuates Schizophrenia-Like Behaviors and Demyelination in a MK-801-Induced Mouse Model of Schizophrenia.

Brain demyelination is possibly one of the main pathological factors involved in schizophrenia, and targeting on myelination may be a useful strategy for schizophrenia treatment. Quetiapine, a widely used atypical antipsychotic drug for schizophrenia treatment, has been reported to have neuroprotective effects on cerebral myelination in a demyelination animal model. The objective of the present study was to evaluate the effect and underlying neuroprotective mechanism of quetiapine on the schizophrenia-like behaviors and possible cerebral demyelination induced by MK-801, an N-methyl-D-aspartate glutamate receptor antagonist. Mice were treated with chronic quetiapine (10 mg/kg/day, intraperitoneally) for 28 days. From day 22 to 28, 1 h after the administration of quetiapine, the mice were administered MK-801 (2 mg/kg/day, subcutaneously). The positive symptom of schizophrenia was measured in a locomotor activity test on day 29, the memory was evaluated by a Y-maze test on day 30, and the sensorimotor gating deficit in mice was measured by prepulse inhibition test on day 31. After the behavioral tests, the protein expression of myelin basic protein (MBP) was measured by Western Blot, and the protein expression of brain-derived neurotrophic factor (BDNF) was measured by ELISA in the frontal cortex of mice. Our results showed quetiapine attenuated schizophrenia-like behaviors including hyperactivity, memory impairment, and sensorimotor gating deficit in the MK-801 mice. In the same time, quetiapine attenuated demyelination, concurrent with attenuated BDNF decrease in the brain of MK-801-injected mice. These results suggest that the beneficial effects of quetiapine on schizophrenia might be partly related to its neuroprotective effect on brain myelin basic protein and its upregulating neuroprotective proteins such as BDNF, and indicate that modulation of cerebral demyelination could be a novel treatment target of schizophrenia.

Lower serum nicotinamide N-methyltransferase levels in patients with bipolar disorder during acute episodes compared to healthy controls: a cross-sectional study.

BACKGROUND: Nicotinamide N-methyltransferase (NNMT) has been implicated in the pathogenesis of neuropsychiatric diseases. Bipolar disorder (BD) is associated with metabolic abnormalities and NNMT regulates energy metabolism and may also exert a causal role in metabolic disorders. The present study aimed to determine serum NNMT levels in patients with BD and compared the results with that of healthy controls, to explore the correlation between NNMT and clinical and metabolic characteristics. METHODS: The NNMT levels of 80 patients having a manic episode of BD and 65 non-psychiatric control individuals were measured using enzyme-linked immunosorbent assay. Metabolic parameters were evaluated using standard laboratory methods. RESULTS: The serum NNMT levels of bipolar mania patients were significantly lower than that of non-psychiatric controls. Furthermore, the serum levels of NNMT were found to be negatively correlated with Young Mania Rating Scale (YMRS) scores and the duration of the illness. Moreover, lower NNMT serum levels were found in patients with a history of antipsychotic medication and dyslipidemia. Our results also demonstrated the different patterns of correlation that exist between the study groups. Serum NNMT levels were found to be negatively correlated with triglyceride, cholesterol, and apolipoprotein B levels in the BD group, while the same was found to be negatively associated only with high-density lipoprotein cholesterol in the control group. CONCLUSIONS: These findings support the suggestion that lower NNMT serum levels are significantly associated with BD and that serum NNMT has the potential to regulate lipid metabolism in BD patients.

Broad-Spectrum Profiling of Drug Safety via Learning Complex Network.

Drug safety is a severe clinical pharmacology and toxicology problem that has caused immense medical and social burdens every year. Regretfully, a reproducible method to assess drug safety systematically and quantitatively is still missing. In this study, we developed an advanced machine learning model for de novo drug safety assessment by solving the multilayer drug-gene-adverse drug reaction (ADR) interaction network. For the first time, the drug safety was assessed in a broad landscape of 1,156 distinct ADRs. We also designed a parameter ToxicityScore to quantify the overall drug safety. Moreover, we determined association strength for every 3,807,631 gene-ADR interactions, which clues mechanistic exploration of ADRs. For convenience, we deployed the model as a web service ADRAlert-gene at http://www.bio-add.org/ADRAlert/. In summary, this study offers insights into prioritizing safe drug therapy. It helps reduce the attrition rate of new drug discovery by providing a reliable ADR profile in the early preclinical stage.

High serum levels of FGF21 are decreased in bipolar mania patients during psychotropic medication treatment and are associated with increased metabolism disturbance.

Bipolar disorder (BD), a psychiatric illness, results partly as a side effect of psychotropic medications and presents a high risk of metabolic disturbance. Fibroblast growth factor 21 (FGF21) is as an important regulator in carbohydrate and lipid metabolism. In this study, we investigated the serum levels of FGF21 and analyzed its association with metabolic parameters in bipolar mania patients at pre- and post-treatment with psychotropic medications. Bipolar mania inpatients (n = 99) and healthy controls (n = 99) were included at baseline; the patients were followed up after four-week treatment. Serum levels of FGF21 and several metabolic parameters were measured by appropriate detection methods. We found that baseline serum FGF21 levels were significantly higher in bipolar manic patients when compared to that in controls. After four-week medication, FGF21 levels were found to be decreased in patients when compared to the baseline suggesting that FGF21 may be associated with the psychopathology of bipolar mania. Moreover, FGF21 levels were found to be negatively correlated with the serum triglycerides (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), glucose (Glu), and Body Mass Index (BMI). In addition, our data also indicates that FGF21 may monitor and/or prevent the metabolic abnormalities induced by psychotropic drugs.